The specific aims of the proposed research are: 1) to identify chemical agents which acutely inhibit replication of hamster buccal pouch keratinocytes (HBPE cells) in vitro, and do not induce resistant cell variants during the period of acute chemical exposure, and 2) to use the chemical agents identified in Specific Aim 1 to select in vitro, and thereby identify and quantitate colonies of HBPE cells which have undergone one or more steps in the carcinogenic process. The proposed assay for initiated HBPE cell is based on the hypothesis that during initiation in vivo, cells acquire a relative resistance to the cytotoxic effects of the inducing carcinogen. The long-range goal of the proposed research is to develop improved strategies for the biological and biochemical characterization of precancerous cells in oral mucosa, and for the early detection and prevention of human oral cancer.